Balance control in stepping down expected and unexpected level changes

Stepping down an elevation in ongoing gait is a common task that can cause falls when the level change is unexpected. The aim of this study was to compare expected and unexpected stepping down. We hypothesized that unexpected stepping would lead to loss of control over the movement and potentially falls due to buckling of the leading leg at landing. Ten male subjects repeatedly walked over a platform on which they stepped down an expected 10-cm height difference. In 5 out of 50 trials, the height difference was encountered unexpectedly early. Kinematics and ground reaction forces under both feet were measured during the stride in which the height difference was negotiated. Stepping down involved a substantial increase in forward horizontal and angular momenta (approximately 40 N s and 20 N ms). In expected stepping down, step length was significantly increased (17%), which allowed control of these forward horizontal and angular momenta immediately following landing. In unexpected stepping down, the time between expected ground contact and actual ground contact (110 ms) appeared too short to substantially adjust leg movement and increase step length. Although buckling of the leg did not occur, presumably due to its more vertical orientation at landing, momentum could not be sufficiently attenuated at landing, but a fall was prevented by a rapid step of the trailing limb. The lack of control of momentum might cause a fall, when the capacity to make such a rapid step falls short, as in the elderly, or when the height difference is larger.     

Effect of a change in step direction from a forward to a lateral target in response to a sensory perturbation

The aim of the current study was to investigate the response of healthy older and young adults to a change in step direction from a forward to a lateral target in response to a sensory perturbation. Nine healthy older (75.1 ± 6.7 years; age range, 65–81 years) and nine young adults (27 ± 3.6 years; age range, 23–31 years) participated in the study. The sensory perturbation was a visual cue presented at random times while subjects stepped over an obstacle from quiet stance. For both young and elderly subjects there was an abrupt change in the slope of both shear ground reaction forces (GRFs) of the stance limb following the perturbation. The slope and peak of the change in GRFs was greater for the young subjects and the onset significantly earlier (205 ms compared to 271 ms). Changes in the GRFs were accompanied by an increase in bilateral gluteus medius and stance limb soleus activity. A late visual cue resulted in a delayed response for elderly subjects. These data show that a stepping response to a sensory perturbation was both delayed and of less magnitude for older adults which has implications for fall risk.     

Characterizing the balance-dexterity task as a concurrent bipedal task to investigate trunk control during dynamic balance

The purpose of the study was to characterize the Balance-Dexterity Task as a means to investigate a concurrent bipedal lower-extremity task and trunk control during dynamic balance. The task combines aspects of single-limb balance and the lower-extremity dexterity test by asking participants to stand on one limb while compressing an unstable spring with the contralateral limb to an individualized target force. Nineteen non-disabled participants completed the study, and performance measures for the demands of each limb – balance and dexterous force control – as well as kinematic and electromyographic measures of trunk control were collected. Given five practice trials, participants achieved compression forces ranging from 100 to 139 N (mean 121.2 ± 12.3 N), representing 14.4–23.0% of body weight (mean 18.7 ± 2.4%), which were then presented as target forces during test trials. Dexterous force control coefficient of variation and average magnitude of the center of pressure (COP) resultant velocity were associated such that greater variability in force control was accompanied by greater COP velocity (R = 0.598, p = 0.007). Trunk coupling, quantified as the coefficient of determination (R²) of a frontal plane thorax and pelvis angle-angle plot, varied independently of any measure of balance or dexterous force control. The Balance-Dexterity Task is a continuous, dynamic balance task where bipedal coordination and trunk coupling can be concurrently observed and studied.     

Muscle response times between shoe and no-shoe conditions following a weight-bearing rotary perturbation are similar in females

The purpose of this study was to compare the muscle response times (MRTs) of select lower extremity muscles following a weight bearing rotary perturbation in single-leg stance with and without shoes. Ten recreationally active females volunteered for this study. Each subject received a rotary perturbation in single-leg stance under two conditions: with shoes and without shoes. The outcomes measured were response times of the medial and lateral quadriceps, hamstrings and gastrocnemius. The results demonstrated that significant differences in MRTs were not apparent for either the medial or lateral perturbation between conditions. While a main effect for muscle was evident for both medial and lateral perturbations, a muscle by shoe interaction was not present for either the medial or lateral perturbation. Our findings suggest that wearing shoes does not alter MRTs during single-limb rotary perturbations. These data indicate that lower extremity perturbation device testing may be done with or without shoes and comparisons between works are permissible as response times are unaffected.     

Characteristics of balance control in older persons who fall with injury – A prospective study

ObjectiveOlder adults who have recently fallen demonstrate increased postural sway compared with non-fallers. However, the differences in postural control between older adults who were seriously injured (SI) as a result of a fall, compared with those who fell but were not injured (NSI) and non-fallers (NFs), has not been investigated. The objective of the present study was to investigate the underlying postural control mechanisms related to injuries resulting from a fall.MethodsBoth traditional postural sway measures of foot center-of-pressure (CoP) displacements and fractal measures, the Stabilogram-Diffusion Analysis (SDA), were used to characterize the postural control. One hundred older adults aged 65–91 years were tested during narrow base upright stance in eyes closed condition; falls were monitored over a 1-year period.ResultsForty-nine older adults fell during the 1-year follow-up, 13 were seriously injured as a result of a fall (SI), 36 were not injured (NSI), and 49 were non-fallers (NFs); two passed away. The SDA showed significantly higher short-term diffusion coefficients and critical displacements in SI in the anterior–posterior direction compared with both NSI and NF. However, in the medio-lateral direction there were no statistically significant differences between groups. For the traditional measures of sway, the average anterior–posterior CoP range was also larger in SI individuals.ConclusionsThis work suggests that older fallers with a deterioration of anterior–posterior postural control may be at higher risk of serious injury following fall events.     

Method for evoking a trip-like response using a treadmill-based perturbation during locomotion

Because trip-related falls account for a significant proportion of falls by patients with amputations and older adults, the ability to repeatedly and reliably simulate a trip or evoke a trip-like response in a laboratory setting has potential utility as a tool to assess trip-related fall risk and as a training tool to reduce fall risk. This paper describes a treadmill-based method for delivering postural perturbations during locomotion to evoke a trip-like response and serve as a surrogate for an overground trip. Subjects walked at a normalized velocity in a Computer Assisted Rehabilitation Environment (CAREN). During single-limb stance, the treadmill belt speed was rapidly changed, thereby requiring the subject to perform a compensatory stepping response to avoid falling. Peak trunk flexion angle and peak trunk flexion velocity during the initial compensatory step following the perturbation were smaller for responses associated with recoveries compared to those associated with falls. These key fall prediction variables were consistent with the outcomes observed for laboratory-induced trips of older adults. This perturbation technique also demonstrated that this method of repeated but randomly delivered perturbations can evoke consistent, within-subject responses.     

Age-related changes in oxidative stress markers and abscisic acid levels in a drought-tolerant shrub, Cistus clusii grown under Mediterranean field conditions

Compared with our knowledge of senescence in annuals and biennials, little is known about age-related changes in perennials. To get new insights into the mechanisms underlying aging in perennials, we measured oxidative stress markers in leaves and organelles, together with abscisic acid levels in leaves of 2- and 7-year-old Cistus clusii dunal plants grown under Mediterranean field conditions. Recently emerged leaves, which either appeared during autumn or spring, were compared to evaluate the effects of environmental constraints on oxidative stress and abscisic acid accumulation as plants aged. Plant aging led to an enhanced oxidation of α-tocopherol and ascorbate, increased lipid peroxidation and reduced PSII efficiency in leaves during the more stressful conditions of spring and summer, but not during autumn. Analyses of lipid peroxidation in organelles isolated from the same leaves revealed that oxidative stress occurred both in chloroplasts and mitochondria. Although both plant groups showed similar leaf water and nitrogen contents throughout the study, abscisic acid levels were markedly higher (up to 75%) in 7-year-old plants compared to 2-year-old plants throughout the study. It is concluded that (a) meristematic tissues of C. clusii maintain the capacity to make new leaves with no symptoms of oxidative stress for several years, unless these leaves are exposed to environmental constraints, (b) leaves of oldest plants show higher oxidative stress than those of young plants when exposed to adverse climatic conditions, thus supporting the idea that the oxidative stress associated with aging is due at least partly to extrinsic factors, (c) at the subcellular level, age-induced oxidative stress occurs both in chloroplasts and mitochondria, and (d) even in the absence of environmental stress, newly emerged leaves accumulate higher amounts of ABA as plants age.     

Age-related changes of beta-endorphin and cholecystokinin in human and rat mononuclear cells

Beta-endorphin (BE) and cholecystokinin (CCK) were measured in fresh PBMC isolated from human subjects and rats. The BE and CCK PBMC contents increased significantly with age both in human and rat models. Moreover, polyclonal stimulation induced a significant decrease of BE but not CCK contents in mononuclear cells from human aged subjects. The time course of changes in BE and CCK concentrations observed in fresh and cultured cells from subjects of different ages did not directly correlate to the time course of age-associated impairment of lectin-induced lymphocyte proliferative response and interleukin-2 synthesis. In fact, the lymphocyte functional defects were significantly observed only in the 71–99 year age group, whereas the neuropeptide changes were already evident in the 31–50 age group. Since BE has been shown to participate in the modulation of the immune system, the age-related modifications of PBMC BE could play a role in the immunodepression observed during aging.     

Age-related changes of hypocretin in basal forebrain of guinea pig

Hypocretin-1 (hcrt-1) and hypocretin-2 (hcrt-2) have been implicated in a wide variety of functions including sleep and wakefulness as well as related behaviors. Many of these functions of the hypocretins involve the activation of cholinergic neurons in the basal forebrain (BF). These neurons have been shown to exhibit age-related changes in a variety of species. In the present experiment, in adult and aged guinea pigs, we compared hypocretin immunoreactivity in regions of the BF that include the medial septal nucleus (MS), the vertical and horizontal limbs of the diagonal band of Broca (VDB and HDB) and the magocellular preoptic nucleus (MCPO). In adult guinea pigs (3–5 months of age), all of the preceding BF regions contained dense hypocretin fibers with varicosities. On the contrary, in old guinea pigs (27–28 months), although the MS exhibited a similar intensity of hypocretin immunoreactivity compared with the adult guinea pig, there was a significant decrease in the intensity of immunoreactivity of hypocretinergic fibers in the VDB, HDB and MCPO. These data indicate that the hypocretinergic innervation of specific nuclei of the BF is compromised during the aging process. We suggest that the reduction in hypocretinergic innervation of the BF nuclei may contribute to the age-related changes in the states of sleep and wakefulness as well as deficits in related systems that occur in old age.     

Age-related changes of serum lipoprotein oxidation in rats

Oxidation of low-density lipoprotein (LDL) may be a prelude to atherogenesis and directly age related. To assess whether there may be relationship between age and plasma lipoprotein (LP) oxidation, we studied copper-mediated LP oxidation isolated from the blood of 2 months, 7 months, and 15 months old rats. We determined whether the susceptibility of LP to oxidation might be related to vitamin C levels in serum, vitamin E levels in LP, or the total antioxidant capacity (TAC) of serum or LP. Serum vitamin C content was inversely related to age, malondialdehyde (MDA) propagation rate, and maximum change of MDA concentrations. However, there were no significant relationships between age and serum TAC, LP TAC, serum vitamin E, or the ratio of LP vitamin E to serum vitamin C content. The lag phase of MDA formation was significantly decreased with age and the ratio of LP vitamin E content to serum vitamin C content, increased with age. Maximum change of MDA concentration was positively correlated with the ratio of LP vitamin E contents to serum vitamin C concentration. Thus, as the rat ages, vitamin C status decreases with an increased LP susceptibility to oxidation. It is tempting to speculate that enhanced LP oxidation in older rats may reflect a reduced amount of recycling of LDL vitamin E by serum vitamin C.     

Age-related changes in brain support cells: Implications for stroke severity

Stroke is one of the leading causes of adult disability and the fourth leading cause of mortality in the US. Stroke disproportionately occurs among the elderly, where the disease is more likely to be fatal or lead to long-term supportive care. Animal models, where the ischemic insult can be controlled more precisely, also confirm that aged animals sustain more severe strokes as compared to young animals. Furthermore, the neuroprotection usually seen in younger females when compared to young males is not observed in older females. The preclinical literature thus provides a valuable resource for understanding why the aging brain is more susceptible to severe infarction. In this review, we discuss the hypothesis that stroke severity in the aging brain may be associated with reduced functional capacity of critical support cells. Specifically, we focus on astrocytes, that are critical for detoxification of the brain microenvironment and endothelial cells, which play a crucial role in maintaining the blood brain barrier. In view of the sex difference in stroke severity, this review also discusses studies of middle-aged acyclic females as well as the effects of the estrogen on astrocytes and endothelial cells.     

Effects of aging in postural strategies during a seated auto-stabilization task

Impaired sensory, motor and central processing systems combining with biomechanical changes are risk of fall factors in the elderly population. The aim of this study was to assess the auto-adaptation and the regulation of the dynamic control of equilibrium in age-related adaptive strategies, by using a seated position on a seesaw. 15 young adults and 12 healthy middle-aged adults were asked to actively maintain a sitting posture as stable as possible during 12.8 s, on a 1-degree of freedom seesaw (auto-stabilization paradigm), with and without vision. The seesaw was placed in order to allow roll or pitch oscillations. We determine length and surfaces CoP shifts, mean positions and variability, a Postural Performance Index (PI) and a Strategy Organization Ratio (SOR). Our results shows that adopted strategies are plane-dependant during auto-stabilization (parallel and perpendicular axes control is impacted) and age-dependant. PI_x during roll seated auto-stabilization tasks appears as the most relevant parameter of aged-related instability. The visual effect, during pitch auto-stabilization, characterizes the postural sensory-motor human behavior. The quantitative and qualitative postural assessment, thanks to seated auto-stabilization task, need to be promoted for long-term health care and probably for the rehabilitation of various disorders.     

Kinetic properties required for sustained or paradoxical control of metabolic fluxes under large changes in enzyme activities

The effect that an increase in the activity of an enzyme has on its flux normally decreases with activity increase. To achieve a large increase in flux by manipulating a single step would therefore require a high initial effect that maintains or increases when the activity is increased, what has been called sustained or paradoxical control. Using metabolic control analysis for large responses, we derive conditions for sustained or paradoxical control in terms of elasticity coefficients. These are used to characterise types of rate laws contributing to this behaviour. The result that simple pathways, with normal kinetics, subject to large activity changes can lead to paradoxical control behaviour suggests that this type of pattern may be much more ubiquitous than could have, in principle, been suspected.     

Stepping threshold with platform-translation and shoulder-pull postural perturbation methods

The type of balance recovery, feet-in-place or stepping, is predicated on the perturbation intensity, often defined by the combination of applied force and displacement. Few studies examined the relationship between characteristics required to produce a stepping response with one of the postural perturbation methods. The purpose of this study was to investigate the relationship between perturbation characteristics (applied force and displacement) required to elicit a forward stepping response with platform-translation and shoulder-pull methods, and to establish whether a common set of perturbation characteristics existed across both perturbation methods. Fourteen young healthy males participated. Temporally unexpected platform translations and shoulder pulls were induced by release of free weights, which fell a controlled height exerting a pull on the platform or on the participant via a shoulder harness. Participants responded with either feet-in-place or stepping responses. The force and displacement were varied to investigate the range of force-displacement combinations required to elicit stepping responses. Force-displacement combinations that elicited stepping responses were recorded and normalized to the participant’s body weight (BW) and the base of support (BOS; participant’s foot length). The lowest force and associated displacement that elicited stepping responses showed an inverse linear relationship during both platform-translation and shoulder-pull trials. The lowest force-displacement combination common to both perturbation methods was found to be 8.75%BW and 105%BOS, which, in the future work, could enable a direct comparison of the neuromuscular and biomechanical responses to different perturbation methods in a manner that attempts to equilibrate the perturbation stimulus across the methods.     

Age-related changes of alpha-crystallin aggregate in human lens

Summary. Lens alpha-crystallin, composed of two subunits alpha A- and alpha B-crystallin, forms large aggregates in the lens of the eye. The present study investigated the aggregate of human lens alpha-crystallin from elderly and young donors. Recombinant alpha A- and alpha B-crystallins in molar ratios of alpha A to alpha B at 1:1, corresponding to the aged sample, were also studied in detail. We found by ultra-centrifugation analysis that the alpha-crystallin aggregate from elderly donors was large and heterogeneous with an average sedimentation coefficient of 30 S and a range of 20–60 S at 37 °C. This was higher compared to the young samples that had an average sedimentation coefficient of 17 S. The sedimentation coefficients of recombinant alpha A- and alpha B-crystallins were approximately 12 S and 15 S, respectively. Even when recombinant alpha-crystallins were mixed in molar ratios equivalent to those found in vivo, similar S values as the native aged alpha-crystallin aggregates were not obtained. Changes in the self-association of alpha-crystallin aggregate were correlated to changes in chaperone activity. Alpha-crystallin from young donors, and recombinant alpha A- and alpha B-crystallin and their mixtures showed chaperone activity, which was markedly lost in samples from the aged alpha-crystallin aggregates.     

Age-related changes in acetylcholinesterase and its molecular forms in various brain areas of rats

A previous study conducted in this laboratory revealed a decrease in total cholinesterase (total ChE) in the cerebral cortex, hippocampus and striatum in aged rats (24 months) of various strains, as compared with young animals (3 months). The purpose of the present experiments was to extend the study to other brain areas (hypothalamus, medulla-pons and cerebellum) and to assess whether this decrease was dependent on the reduction of either specific acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE) or both. By using ultracentrifugation on a sucrose gradient, the molecular forms of AChE were evaluated in all the brain areas of young and aged Sprague-Dawley rats. In young rats the regional distribution of total ChE and AChE varied considerably with respect to BuChE. The age-related loss of total ChE was seen in all areas. Although there was a reduction of AChE and, to somewhat lesser extent, of BuChE in the cerebral cortex, hippocampus, striatum, and hypothalamus (but not in the medulla-pons or the cerebellum), the ratio AChE/BuChE was not substantially modified by age. Two molecular forms of AChE, namely G4 (globular tetrameric) and G1 (monomeric), were detected in all the brain areas. Their distribution, expressed as G4/G1 ratio, varied in young rats from about 7.5 for the striatum to about 2.0 for the medulla-pons and cerebellum. The age-related changes consisted in a significant and selective loss of the enzymatic activity of G4 forms in the cerebral cortex, hippocampus, striatum, and hypothalamus, which resulted in a significant decrease of the G4/G1 ratio. No such changes were found in the medullapons or the cerebellum. Since G4 forms have been proposed to be present presynaptically, their age-related loss in those brain areas where acetylcholine plays an important role in neurotransmission may indicate an impairment of presynaptic mechanisms.     

Age-related changes in the metabolization of phosphatidic acid in rat cerebral cortex synaptosomes

In this study, phosphatidic acid (PA) metabolization is found to generate diacylglycerol (DAG), monoacylglycerol (MAG) and glycerol by the sequential action of lipid phosphate phosphatase (LPP), diacylglycerol lipase (DAGL), and monoacylglycerol lipase (MAGL) in cerebral cortex (CC) synaptosomes. It is also demonstrated that PA is metabolized by phospholipases A (PLA)/lysophosphatidic acid phosphohydrolase (LPAPase) in synaptic endings. Age-related changes in the metabolization of PA have been observed in rat cerebral cortex synaptosomes in the presence of the alternative substrates for LPP, namely LPA, sphingosine 1-phosphate (S1P) and ceramide 1-phosphate (C1P). In addition, LPA and C1P up to concentrations of about 50 μM favor the metabolism in the direction of MAG and glycerol in aged and adult synaptosomes, respectively. At equimolecular concentrations with PA, LPA decreases DAG formation in adult and aged synaptosomes, whereas S1P decreases it and C1P increases it only in aged synaptosomes. Sphingosine (50 μM) or ceramide (100 μM) increase PA metabolism by the pathway that involves LPP/DAGL/MAGL action in aged membranes. Using RHC-80267, a DAGL inhibitor, we could observe that 50% and 33% of MAG are produced as a result of DAGL action in adult and aged synaptosomes, respectively. Taken together, our findings indicate that the ageing modifies the different enzymatic pathways involved in PA metabolization.     

The assessment of posture control in the elderly using the displacement of the center of pressure after forward platform translation

We investigated the change of the center of pressure (COP) after forward platform translations in healthy subjects. These studies were performed on 26 normal young subjects and 20 healthy elderly subjects, who had a normal neurologic examination. Subjects stood barefoot on a three dimensional force plate on the platform, with feet parallel. The duration of the forward platform translations was 0.15 s, and the displacements were 3.75, 7.5, 10, 15, 20, and 30 mm. Six trials were carried out at random. The COP data were recorded for 35 s during standing, and were analyzed for 5 s after translation. With the platform translation displacements from 3.75 to 15 mm, displacement of the COP showed a tendency to increase in all subjects. Whereas with the stimuli between 20 and 30 mm, the results were more varied. The elderly group showed significantly (p<0.05) larger sway than the young group. These results indicate that the individual ability of posture control may be assessed by means of measuring the sway of the center of gravity after platform translation. Electromyography was carried out simultaneously, it showed that elderly people contrary to young subjects used proximal biceps femoris and distal foot muscles at an early stage of the platform translation (p<0.05), suggesting lack of ankle stability with aging.     

Age-related changes of Alzheimer's disease-associated proteins in cynomolgus monkey brains

We characterized senile plaques (SPs) immunohistochemically in cynomolgus monkey brains and also examined age-related biochemical changes of Alzheimer's disease (AD)-associated proteins in these brains from monkeys of various ages. In the neocortex of aged monkeys (>20 years old), we found SPs but no neurofibrillary tangles (NFTs). Antibodies against beta-amyloid precursor protein (APP) or apolipoprotein E (ApoE) stained SPs; however, the pattern of immunostaining was different for the two antigens. APP was present only in swollen neurites, but ApoE was present throughout all parts of SPs. Western blot analysis revealed that the pattern of APP expression changed with age. Although full-length APP695 protein was mainly expressed in brains from young monkeys (4-years-old), the expression of full-length APP751 protein was increased in brains from older monkeys (>20 years old). Biochemical analyses also showed that levels of various AD-associated proteins increased significantly with age in nerve ending fractions. Both SP-associated (APP) and NFT-associated proteins (tau, activated glycogen synthase kinase 3beta, cyclin dependent kinase 5, p35, and p25) accumulated in the nerve ending fraction with increasing age; however, we found no NFTs or paired helical filaments of tau in aged cynomolgus monkey brains. This age-related accumulation of these proteins in the nerve ending fraction was similar to that observed in our laboratory previously for presenilin-1 (PS-1). The accumulation of these SP-associated proteins in this fraction may be a causal event in the spontaneous formation of SPs; thus, SPs may be formed initially in nerve endings. Taken together, these results suggest that intensive investigation of age-related changes in the nerve ending and in axonal transport will contribute to a better understanding of the pathogenesis of neurodegenerative disorders such as AD.     

猫初级视皮层内GIu/GABA表达比率的衰老性变化

最近的一些研究结果显示,视皮层内抑制性递质系统作用减弱可能是导致老年性视觉功能衰退的重要因素.是否皮层内兴奋性递质系统亦伴随衰老而发牛改变并影响皮层内神经兴奋与抑制的平衡尚不清楚.为此,利用Nissl染色和免疫组织化学染色方法以及Image-Pro Express图像分析软件对青、老年猫初级视皮层(17区)内各层神经元密度、兴奋性递质谷氨酸免疫反应阳性(Glu-immunoreactive,Glu-IR)神经元密度以及抑制性递质γ-氨基丁酸免疫反应阳性(γ-aminobutyric acid.immunoreactive,GABA-IR)神经元密度进行了统汁分析.结果显示,青、老年猫初级视皮层各层神经元密度均没有明显的年龄性差异(P>0.05);与青年猫相比,老年猫初级视皮层Glu-IR、GABA-IR神经元密度均显著减少(P<0.01),而Glu.IR/GABA.IR神经元密度比率去却显著增大(P<0.01).结果提示,老年猫初级视皮层内兴奋性递质系统作用相对增强,而抑制性递质系统的作用相对减弱,导致皮层内兴奋-抑制平衡关系失调,这可能是引起老年个体视觉功能衰退的重要原因之一.